Pharmalogical Challenge Models

CHDR

CHDR has grown over the past 30 years. with a strategy of thorough functional testing for pharmacological effects in early clinical drug research. An important tool to look for pharmacological effect even in healthy subjects are various pharmacological challenges. We have an experienced CNS research group, with a self funded research line focusing on development and validation of models that help to answer important research questions of our sponsors.

Ketamine challenge

The psychoactive properties of several classes of drugs can be used to induce psychomimetic symptoms in healthy volunteers as a model for psychosis and antipsychotic drug action. Previous studies have used THC for this.

A ketamine-challenge was found to be a robust method to induce psychomimetic symptoms, that could be measured by the PANSS, prepulse inhibition and VAS. The response was larger than the response found for the THC-challenge and there were no 'non-responders'.

Mitochondrial function challenge (statin induced)

Evidence has shown that dysfunction of mitochondria plays an important role in age related diseases, such as diabetes mellitus type 2, sarcopenia, and most neurodegenerative diseases. We have validated a model for statin-induced mitochondrial dysfunction in healthy subjects, which can be used to evaluate the pharmacodynamic effects of drugs that potentially enhance mitochondrial function.

THC challenge

CHDR has a long tradition in investigating THC, the active compound of cannabis, which resulted in a robust PK/PD model. THC induces psychomimetic symptoms that closely resemble core aspects of acute clinical psychosis. In clinical research, psychotic symptoms are often quantified with the Positive and Negative Syndrome Scale (PANSS). From this instrument, CHDR has developed a repeatable, reproducible, dose dependent and clinically relevant structured interview. The positive PANSS shows highly significant dose-dependent psychotic effects of THC in a majority of healthy volunteers.

They may be used as primary read-out parameters for neurotransmitter activation (with challenge-tests using 5-HTP, metoclopramine or desmopressin) or modulation of central neurotransmission, or to assess general neuroendocrine effects of novel drugs.

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Neurology

CHDR is contributing to the development of new drugs against neurodegeneration. We are developing biomarkers to demonstrate a compound’s effects in healthy volunteers, and at the same time we are expanding our abilities to perform research in patients with Alzheimer’s disease and other neurodegenerative diseases, such as Multiple Sclerosis, Parkinson's Disease or epilepsy. CHDR’s staff includes two board-certified neurologists with clinical positions in academic medical hospitals in Leiden and Amsterdam.